Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Mingus · Oct 10, 2006

[SIZE=-1]http://ajrccm.atsjournals.org/cgi/content/abstract/200604-561OCv1
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[SIZE=-1]Submitted on April 24, 2006[/SIZE]
[SIZE=-1]Accepted on October 5, 2006[/SIZE]

Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Clinton S Robbins1, Carla M.T. Bauer2, Neda Vujicic2, Gordon J Gaschler2, Brian D Lichty2, Earl G Brown3, and Martin R Stampfli4* 1 Department of Pathology and Molecular Medicine, McMaster University, Centre for Gene Therapeutics, Hamilton, Ontario, Canada; Department of Biology, McMaster University, Hamilton, Ontario, Canada, 2 Department of Pathology and Molecular Medicine, McMaster University, Centre for Gene Therapeutics, Hamilton, Ontario, Canada, 3 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada, 4 Department of Pathology and Molecular Medicine, McMaster University, Centre for Gene Therapeutics, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada
* To whom correspondence should be addressed. E-mail: stampfli@mcmaster.ca<script type="text/javascript"></script>.
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Rationale: Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents. Objective: The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden following respiratory infection with influenza A. Methods: C57BL/6 mice were sham- or smoke-exposed for three to five months and infected with either 2.5x103 pfu (low dose) or 2.5x105 pfu (high dose) influenza virus. Measurements and Main Results: While smoke exposure attenuated the airways inflammatory response to low dose infection, we observed increased inflammation in smoke- compared to sham-exposed mice following infection with high dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of TNF

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, IL-6 and type 1 interferon in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral re-challenge. Conclusion: Our study suggests that in mice cigarette smoke affects primary antiviral immune-inflammatory responses, while secondary immune protection remains intact.
 
Key words: Chronic Obstructive Pulmonary Disease, Immunity, Inflammation, Neutrophils

Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

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